Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infection

PLoS ONE

Volumn 6, Issue 1, 2011, Pages

  Barroso, Helena ^a,b   Borrego, Pedro ^a   Bártolo, Inês ^a,b   Marcelino, José Maria ^c   Família, Carlos ^b   Quintas, Alexandre ^b   Taveira, Nuno ^a,b,d  

^a RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

^b INSTITUTO SUPERIOR DE CIÊNCIAS DA SAÚDE EGAS MONIZ   (Portugal)

^c INSTITUTO DE HIGIENE E MEDICINA TROPICAL   (Portugal)

^d INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; GLYCOPROTEIN GP 120; HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN; NEUTRALIZING ANTIBODY;

ARTICLE; CONTROLLED STUDY; DNA SEQUENCE; EVOLUTIONARY DEVELOPMENTAL BIOLOGY; EVOLUTIONARY RATE; GENETIC VARIABILITY; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS 2 INFECTION; IMMUNOMODULATION; IN VIVO STUDY; MICROBIAL DIVERSITY; MOLECULAR EVOLUTION; NONHUMAN; NUCLEOTIDE SEQUENCE; PHYLOGENETIC TREE; PROCESS MODEL; RECEPTOR BINDING; SPECIES DIFFERENCE; STRUCTURE ANALYSIS; VIRUS CELL INTERACTION; VIRUS ENVELOPE; VIRUS MORPHOLOGY; VIRUS TRANSMISSION; CHEMISTRY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PROTEIN CONFORMATION;

HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2;

ANTIBODIES, NEUTRALIZING; EPITOPES; EVOLUTION, MOLECULAR; HIV ANTIGENS; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HIV-2; HUMANS; PROTEIN CONFORMATION;

EID: 79251624890     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0014548     Document Type: Article

References (101)

1. Zhang M, Foley B, Schultz AK, Macke JP, Bulla I, et al. (2010) The role of recombination in the emergence of a complex and dynamic HIV epidemic. Retrovirology 7: 25.
2. Lemey P, Pybus OG, Wang B, Saksena NK, Salemi M, et al. (2003) Tracing the origin and history of the HIV-2 epidemic. Proc Natl Acad Sci U S A 100: 6588-6592.
3. de Silva TI, Cotten M, Rowland-Jones SL (2008) HIV-2: the forgotten AIDS virus. Trends Microbiol 16: 588-595.
4. Semaille C, Barin F, Cazein F, Pillonel J, Lot F, et al. (2007) Monitoring the dynamics of theHIV epidemic using assays for recent infection and serotyping among new HIV diagnoses: experience after 2 years in France. J Infect Dis 196: 377-383.
5. Valadas E, Franca L, Sousa S, Antunes F (2009) 20 years of HIV-2 infection in Portugal: trends and changes in epidemiology. Clin Infect Dis 48: 1166-1167.
6. Gao F, Yue L, Robertson DL, Hill SC, Hui H, et al. (1994) Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology. J Virol 68: 7433-7447.
7. Chen Z, Luckay A, Sodora DL, Telfer P, Reed P, et al. (1997) Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus-infected sooty mangabeys. J Virol 71: 3953-3960.
8. Yamaguchi J, Devare SG, Brennan CA (2000) Identification of a new HIV-2 subtype based on phylogenetic analysis of full-length genomic sequence. AIDS Res Hum Retroviruses 16: 925-930.
9. Damond F, Worobey M, Campa P, Farfara I, Colin G, et al. (2004) Identification of a highly divergent HIV type 2 and proposal for a change in HIV type 2 classification. AIDS Res Hum Retroviruses 20: 666-672.
10. Rowland-Jones S (2006) Protective immunity against HIV infection: lessons from HIV-2 infection. Future Microbiol 1: 427-433.
11. Berry N, Ariyoshi K, Jaffar S, Sabally S, Corrah T, et al. (1998) Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection. J Hum Virol 1: 457-468.
12. Soares R, Foxall R, Albuquerque A, Cortesao C, Garcia M, et al. (2006) Increased frequency of circulating CCR5+ CD4+ T cells in human immunodeficiency virus type 2 infection. J Virol 80: 12425-12429.
13. Marlink R, Kanki P, Thior I, Travers K, Eisen G, et al. (1994) Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 265: 1587-1590.
14. Drylewicz J, Matheron S, Lazaro E, Damond F, Bonnet F, et al. (2008) Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France. AIDS 22: 457-468.
15. Rodriguez SK, Sarr AD, MacNeil A, Thakore-Meloni S, Gueye-Ndiaye A, et al. (2007) Comparison of heterologous neutralizing antibody responses of human immunodeficiency virus type 1 (HIV-1)- and HIV-2-infected Senegalese patients: distinct patterns of breadth and magnitude distinguish HIV-1 and HIV-2 infections. J Virol 81: 5331-5338.
16. Lizeng Q, Skott P, Sourial S, Nilsson C, Andersson SS, et al. (2003) Serum immunoglobulin A (IgA)-mediated immunity in human immunodeficiency virus type 2 (HIV-2) infection. Virology 308: 225-232.
17. Shi Y, Brandin E, Vincic E, Jansson M, Blaxhult A, et al. (2005) Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J Gen Virol 86: 3385-3396.
18. Bjorling E, Scarlatti G, von Gegerfelt A, Albert J, Biberfeld G, et al. (1993) Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. Virology 193: 528-530.
19. Cavaleiro R, Sousa AE, Loureiro A, Victorino RM (2000) Marked immunosuppressive effects of the HIV-2 envelope protein in spite of the lower HIV-2 pathogenicity. AIDS 14: 2679-2686.
20. Cavaleiro R, Brunn GJ, Albuquerque AS, Victorino RM, Platt JL, et al. (2007) Monocyte-mediated T cell suppression by HIV-2 envelope proteins. Eur J Immunol 37: 3435-3444.
21. Grossman Z, Meier-Schellersheim M, Sousa AE, Victorino RM, Paul WE (2002) CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause? Nat Med 8: 319-323.
22. Blaak H, van der Ende ME, Boers PH, Schuitemaker H, Osterhaus AD (2006) In vitro replication capacity of HIV-2 variants from long-term aviremic individuals. Virology 353: 144-154.
23. MacNeil A, Sarr AD, Sankale JL, Meloni ST, Mboup S, et al. (2007) Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol 81: 5325-5330.
24. Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, et al. (1998) The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393: 705-711.
25. Douagi I, Forsell MN, Sundling C, O'Dell S, Feng Y, et al. (2009) Influence of Novel CD4 binding-defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T Cell Responses in Non-human Primates. J Virol.
26. Moore JP, Willey RL, Lewis GK, Robinson J, Sodroski J (1994) Immunological evidence for interactions between the first, second, and fifth conserved domains of the gp120 surface glycoprotein of human immunodeficiency virus type 1. J Virol 68: 6836-6847.
27. Hwang SS, Boyle TJ, Lyerly HK, Cullen BR (1991) Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science 253: 71-74.
28. Rizzuto CD, Wyatt R, Hernandez-Ramos N, Sun Y, Kwong PD, et al. (1998) A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280: 1949-1953.
29. Javaherian K, Langlois AJ, McDanal C, Ross KL, Eckler LI, et al. (1989) Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A 86: 6768-6772.
30. Javaherian K, Langlois AJ, LaRosa GJ, Profy AT, Bolognesi DP, et al. (1990) Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science 250: 1590-1593.
31. Krachmarov CP, Honnen WJ, Kayman SC, Gorny MK, Zolla-Pazner S, et al. (2006) Factors determining the breadth and potency of neutralization by V3- specific human monoclonal antibodies derived from subjects infected with clade A or clade B strains of human immunodeficiency virus type 1. Journal of Virology 80: 7127-7135.
32. Davis KL, Bibollet-Ruche F, Li H, Decker JM, Kutsch O, et al. (2009) Human immunodeficiency virus type 2 (HIV-2)/HIV-1 envelope chimeras detect high titers of broadly reactive HIV-1 V3-specific antibodies in human plasma. J Virol 83: 1240-1259.
33. Forsell MN, Schief WR, Wyatt RT (2009) Immunogenicity of HIV-1 envelope glycoprotein oligomers. Curr Opin HIV AIDS 4: 380-387.
34. Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, et al. (2009) Broad diversity of neutralizing antibodies isolated from memory B cells in HIVinfected individuals. Nature 458: 636-640.
35. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326: 285-289.
36. Traincard F, Rey-Cuille MA, Huon I, Dartevelle S, Mazie JC, et al. (1994) Characterization of monoclonal antibodies to human immunodeficiency virus type 2 envelope glycoproteins. AIDS Res Hum Retroviruses 10: 1659-1667.
37. Bjorling E, Broliden K, Bernardi D, Utter G, Thorstensson R, et al. (1991) Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity. Proc Natl Acad Sci U S A 88: 6082-6086.
38. Bjorling E, Chiodi F, Utter G, Norrby E (1994) Two neutralizing domains in the V3 region in the envelope glycoprotein gp125 of HIV type 2. J Immunol 152: 1952-1959.
39. McKnight A, Shotton C, Cordell J, Jones I, Simmons G, et al. (1996) Location, exposure, and conservation of neutralizing and nonneutralizing epitopes on human immunodeficiency virus type 2 SU glycoprotein. J Virol 70: 4598-4606.
40. Morner A, Achour A, Norin M, Thorstensson R, Bjorling E (1999) Fine characterization of a V3-region neutralizing epitope in human immunodeficiency virus type 2. Virus Res 59: 49-60.
41. Matsushita S, Matsumi S, Yoshimura K, Morikita T, Murakami T, et al. (1995) Neutralizing monoclonal antibodies against human immunodeficiency virus type 2 gp120. J Virol 69: 3333-3340.
42. Marcelino JM, Borrego P, Rocha C, Barroso H, Quintas A, et al. (2010) Potent and broadly reactive HIV-2 neutralizing antibodies elicited by a vaccinia virus vector prime-C2V3C3 polypeptide boost immunization strategy. J Virol 84: 12429-12436.
43. Plantier JC, Damond F, Souquieres S, Brun-Vezinet F, Simon F, et al. (2001) V3 serological subtyping of human immunodeficiency virus type 2 infection is not relevant. J Clin Microbiol 39: 3803-3807.
44. Marcelino JM, Nilsson C, Barroso H, Gomes P, Borrego P, et al. (2008) Envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is associated with disease progression. AIDS 22: 2257-2265.
45. Marcelino JM, Barroso H, Goncalves F, Silva SM, Novo C, et al. (2006) Use of a new dual-antigen enzyme-linked immunosorbent assay to detect and characterize the human antibody response to the human immunodeficiency virus type 2 envelope gp125 and gp36 glycoproteins. J Clin Microbiol 44: 607-611.
46. Huang ML, Essex M, Lee TH (1991) Localization of immunogenic domains in the human immunodeficiency virus type 2 envelope. J Virol 65: 5073-5079.
47. Frost SD, Wrin T, Smith DM, Kosakovsky Pond SL, Liu Y, et al. (2005) Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection. Proc Natl Acad Sci U S A 102: 18514-18519.
48. Lemey P, Rambaut A, Pybus OG (2006) HIV evolutionary dynamics within and among hosts. AIDS Rev 8: 125-140.
49. Liang B, Luo M, Ball TB, Plummer FA (2007) QUASI analysis of the HIV-1 envelope sequences in the Los Alamos National Laboratory HIV sequence database: pattern and distribution of positive selection sites and their frequencies over years. Biochem Cell Biol 85: 259-264.
50. Canducci F, Marinozzi MC, Sampaolo M, Berre S, Bagnarelli P, et al. (2009) Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects. Retrovirology 6: 4.
51. Antunes R, Figueiredo S, Bartolo I, Pinheiro M, Rosado L, et al. (2003) Evaluation of the clinical sensitivities of three viral load assays with plasma samples from a pediatric population predominantly infected with human immunodeficiency virus type 1 subtype G and BG recombinant forms. J Clin Microbiol 41: 3361-3367.
52. Borrego P, Marcelino JM, Rocha C, Doroana M, Antunes F, et al. (2008) The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients. Retrovirology 5: 78.
53. Esteves A, Parreira R, Venenno T, Franco M, Piedade J, et al. (2002) Molecular epidemiology of HIV type 1 infection in Portugal: high prevalence of non-B subtypes. AIDS Res Hum Retroviruses 18: 313-325.
54. Palma AC, Araujo F, Duque V, Borges F, Paixao MT, et al. (2007) Molecular epidemiology and prevalence of drug resistance-associated mutations in newly diagnosed HIV-1 patients in Portugal. Infect Genet Evol 7: 391-398.
55. Korber BT, Kunstman KJ, Patterson BK, Furtado M, McEvilly MM, et al. (1994) Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J Virol 68: 7467-7481.
56. De Jong JJ, De Ronde A, Keulen W, Tersmette M, Goudsmit J (1992) Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol 66: 6777-6780.
57. Resch W, Hoffman N, Swanstrom R (2001) Improved success of phenotype prediction of the human immunodeficiency virus type 1 from envelope variable loop 3 sequence using neural networks. Virology 288: 51-62.
58. Isaka Y, Sato A, Miki S, Kawauchi S, Sakaida H, et al. (1999) Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5. Virology 264: 237-243.
59. Skar H, Borrego P, Wallstrom TC, Mild M, Marcelino JM, et al. (2010) HIV-2 genetic evolution in patients with advanced disease is faster than in matched HIV-1 patients. J Virol 84: 7412-7415.
60. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, et al. (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393: 648-659.
61. Soriano V, Gomes P, Heneine W, Holguin A, Doruana M, et al. (2000) Human immunodeficiency virus type 2 (HIV-2) in Portugal: clinical spectrum, circulating subtypes, virus isolation, and plasma viral load. J Med Virol 61: 111-116.
62. Barroso H, Taveira N (2005) Evidence for negative selective pressure in HIV-2 evolution in vivo. Infect Genet Evol 5: 239-246.
63. Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, et al. (2007) Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445: 732-737.
64. Moore PL, Gray ES, Choge IA, Ranchobe N, Mlisana K, et al. (2008) The c3- v4 region is a major target of autologous neutralizing antibodies in human immunodeficiency virus type 1 subtype C infection. J Virol 82: 1860-1869.
65. Rong R, Gnanakaran S, Decker JM, Bibollet-Ruche F, Taylor J, et al. (2007) Unique mutational patterns in the envelope alpha 2 amphipathic helix and acquisition of length in gp120 hypervariable domains are associated with resistance to autologous neutralization of subtype C human immunodeficiency virus type 1. J Virol 81: 5658-5668.
66. Gaschen B, Taylor J, Yusim K, Foley B, Gao F, et al. (2002) Diversity considerations in HIV-1 vaccine selection. Science 296: 2354-2360.
67. Choisy M, Woelk CH, Guegan JF, Robertson DL (2004) Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes. J Virol 78: 1962-1970.
68. Pond SL, Frost SD, Grossman Z, Gravenor MB, Richman DD, et al. (2006) Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol 2: e62.
69. Pybus OG, Rambaut A, Belshaw R, Freckleton RP, Drummond AJ, et al. (2007) Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution. Mol Biol Evol 24: 845-852.
70. Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, et al. (2004) Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303: 2019-2022.
71. Lemey P, Kosakovsky Pond SL, Drummond AJ, Pybus OG, Shapiro B, et al. (2007) Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. PLoS Comput Biol 3: e29.
72. Huang CC, Tang M, Zhang MY, Majeed S, Montabana E, et al. (2005) Structure of a V3-containing HIV-1 gp120 core. Science 310: 1025-1028.
73. Pinter A (2007) Roles of HIV-1 Env variable regions in viral neutralization and vaccine development. Curr HIV Res 5: 542-553.
74. Binley J (2009) Specificities of broadly neutralizing anti-HIV-1 sera. Curr Opin HIV AIDS 4: 364-372.
75. Tomaras GD, Haynes BF (2009) HIV-1-specific antibody responses during acute and chronic HIV-1 infection. Curr Opin HIV AIDS 4: 373-379.
76. Selvarajah S, Puffer BA, Lee FH, Zhu P, Li Y, et al. (2008) Focused dampening of antibody response to the immunodominant variable loops by engineered soluble gp140. AIDS Res Hum Retroviruses 24: 301-314.
77. Garrity RR, Rimmelzwaan G, Minassian A, Tsai WP, Lin G, et al. (1997) Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope. J Immunol 159: 279-289.
78. Kim YB, Han DP, Cao C, Cho MW (2003) Immunogenicity and ability of variable loop-deleted human immunodeficiency virus type 1 envelope glycoproteins to elicit neutralizing antibodies. Virology 305: 124-137.
79. Skott P, Achour A, Norin M, Thorstensson R, Bjorling E (1999) Characterization of neutralizing sites in the second variable and fourth variable region in gp125 and a conserved region in gp36 of human immunodeficiency virus type 2. Viral Immunol 12: 79-88.
80. Mota-Miranda A, Gomes H, Lima-Alves C, Araujo F, Cunha-Ribeiro LM, et al. (2001) Perinatally acquired HIV-2 infection diagnosed at 15 and 24 years of age. AIDS 15: 2460-2461.
81. Leitner T, Escanilla D, Marquina S, Wahlberg J, Brostrom C, et al. (1995) Biological and molecular characterization of subtype D, G, and A/D recombinant HIV-1 transmissions in Sweden. Virology 209: 136-146.
82. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25: 4876-4882.
83. Posada D, Crandall KA (1998) MODELTEST: testing the model of DNA substitution. Bioinformatics 14: 817-818.
84. Rodriguez F, Oliver JL, Marin A, Medina JR (1990) The general stochastic model of nucleotide substitution. J Theor Biol 142: 485-501.
85. Posada D (2003) Using Modeltest and PAUP* to select a model of nucleotide substitution. In: A. D. Baxevanis DBD, R. D. M. Page et al, eds. Current Protocols in Bioinformatics. Chichester, UK: John Wiley & Sons, Inc. pp 6.5.1-6.5.14.
86. Swofford DL (1998) PAUP*. Phylogenetic Analysis using Parsimony (*and other Methods). Version 4. Version 4 ed. SunderlandMA: Sinauer-Associates.
87. Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SD (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23: 1891-1901.
88. Pond SL, Frost SD (2005) Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21: 2531-2533.
89. Zhang M, Gaschen B, Blay W, Foley B, Haigwood N, et al. (2004) Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14: 1229-1246.
90. Pond SL, Frost SD, Muse SV (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21: 676-679.
91. Muse SV, Gaut BS (1994) A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol 11: 715-724.
92. Kosakovsky Pond SL, Poon AWF, Frost SDW (2009) Estimating selection pressures on aligments of coding sequences: practice. In: Lemey P, Salemi M, Vandamme A, eds. The Phylogenetic Handbook: A Paratical Approach to Phylogenetic Analysis and Hypothesis Testing, 2nd ed. Cambridge, UK: Cambridge University Press. pp 452-490.
93. Kosakovsky Pond SL, Frost SD (2005) Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22: 1208-1222.
94. Pond SK, Muse SV (2005) Site-to-site variation of synonymous substitution rates. Mol Biol Evol 22: 2375-2385.
95. Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22: 195-201.
96. Kiefer F, Arnold K, Kunzli M, Bordoli L, Schwede T (2009) The SWISSMODEL Repository and associated resources. Nucleic Acids Res 37: D387-392.
97. Peitsch MC (1995) Protein Modeling by E-mail. Nature Biotechnology 13: 658-660.
98. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18: 2714-2723.
99. Accelrys Inc (2008) Discovery Studio 2.1. San DiegoCA: Accelrys Inc.
100. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera, a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
101. Gerstein M (1992) A Resolution-Sensitive Procedure for Comparing Protein Surfaces and its Application to the Comparison of Antigen-Combining Sites. Acta Cryst A48: 271-276.